This proposal represents a one year project designed to estimate the rate of 5-hydroxytryptamine (5-HT) synthesis in the maturing brain of the mouse and compare it to the abult brain. There is evidence to indicate that 5-HT is synthesized in the immature brain at a rate faster than measurements of enzymes and 5-HT stores have suggested. There is also reason to believe that limited storage sites in immature brain results in rapid conversion of much newly made 5-HT directly to 5-hydroxyindole acetic acid (5-HIAA). Direct measurement of indoleamine synthesis during the maturational period has not been made. Although a number of methods are available for measuring rate of 5-HT synthesis in adult brain, we have evidence that some of them cannot be used on the neonatal brain. The use of drugs to block enzyme action followed by an estimation of substrate buildup has been used in adult brain and will be used here for maturing brain. We will block 5-hydroxytryptophan decarboxylase (5-HTD) with the inhibitor NSD 1015 and assay for 5-hydroxytryptophan (5-HTP) accumulation, and we will block monoamine oxidase (MAO) with the MAO inhibitor pargyline and assay for 5-HT accumulation. Established methods of differential extraction followed by fluorometric assay will be used to measure these intermediates. Mice of various ages between birth and adulthood will be used for these experiments and two brain fractions, the cerebral hemispheres and the brain stem, will be measured.